Prolactin

prolactin, also called luteotropic hormone (LTH) or luteotropin,
a proteinhormone produced by the pituitary gland of mammals that acts with other hormones to initiate secretion of milk by the mammary glands. On the evolutionary scale, prolactin is an ancient hormone serving multiple roles in mediating the care of progeny (sometimes called the “parenting” hormone). It is a large protein molecule that is synthesized in and secreted from lactotrophs, which constitute about 20 percent of the anterior pituitary gland and are located largely in the lateral regions of the gland.

Physiological importance of prolactin

In women the major action of prolactin is to initiate and sustain lactation. In breast-feeding mothers, tactile stimulation of the nipples and the breast by the suckling infant blocks the secretion of hypothalamic dopamine (which normally inhibits prolactin) into the hypophyseal-portal circulation of the pituitary gland. This results in a sharp rise in serum prolactin concentrations, followed by a prompt fall when feeding stops. High serum prolactin concentrations inhibit secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, thereby decreasing the secretion of gonadotropins (luteinizing hormone and follicle-stimulating hormone), and may also inhibit the action of gonadotropins on the gonads. Thus, high serum prolactin concentrations during lactation reduce fertility, protecting lactating women from a premature pregnancy.

Because prolactin acts to maintain the corpus luteum of the ovary, which is the source of the female sex hormone progesterone, it helps to sustain pregnancy. In addition, prolactin secretion increases progressively during pregnancy. The secretion of prolactin also can be stimulated by high doses of estrogens, and it is transiently stimulated by stress and exercise. The function of prolactin in males is not known.

Regulation of prolactin secretion

The hypothalamic regulation of prolactin secretion by the anterior pituitary gland is different from the hypothalamic regulation of other pituitary hormones in two respects. First, hypothalamic control of prolactin secretion is primarily inhibitory, whereas the hypothalamic control of the secretion of other anterior pituitary hormones is stimulatory. Thus, if the anterior pituitary is separated from the influence of the hypothalamus, the secretion of prolactin increases whereas that of the other anterior pituitary hormones decreases. The hypothalamic factor that inhibits prolactin secretion is the neurotransmitterdopamine, which is not a neuropeptide, as are the other hypothalamic hormones that regulate anterior pituitary hormone secretion. Drugs that mimic the action of dopamine are therefore useful in treating patients with high serum prolactin concentrations.

Prolactin-stimulating factors also exist, and included among them are GnRH, thyrotropin-releasing hormone, and vasoactive intestinal polypeptide. However, the physiologic importance of these prolactin-stimulating factors is not well-defined. One example of a prolactin-stimulating factor for which a role has been identified is estrogen, which stimulates prolactin synthesis and secretion in the late stages of pregnancy to prepare the mammary glands for lactation.

Prolactin deficiency and excess

Prolactin deficiency occurs as a result of general pituitary hormone deficiency, which is characterized by the deficiency of other pituitary hormones in addition to prolactin. A primary cause of pituitary hormone deficiency is a pituitary tumour. The most striking example of prolactin deficiency is that of Sheehan syndrome, in which the anterior pituitary gland of pregnant women is partly or totally destroyed during or shortly after giving birth. This syndrome tends to occur more frequently in women who have excessive bleeding during delivery. Affected women do not produce breast milk and cannot nurse their infants. Prolactin deficiency does not cause abnormalities in women who are not trying to nurse their infants and does not cause abnormalities in men.

Increased prolactin secretion can be caused by damage to the pituitary stalk, thereby interrupting the flow of dopamine from the hypothalamus through the hypophyseal-portal circulation to the lactotrophs. In addition, increased prolactin secretion may be caused by prolactin-producing pituitary tumours, such as lactotroph adenomas or prolactinomas, and by several systemic diseases, notably thyroid deficiency. Many drugs, particularly those used for the treatment of psychological or psychiatric disorders, high blood pressure (hypertension), and pain may also increase prolactin secretion. In some patients with high serum prolactin concentrations (hyperprolactinemia), however, no cause is discernible, and they are said to have idiopathic hyperprolactinemia.

In women of reproductive age, high serum prolactin concentrations result in decreased secretion of gonadotropins and therefore decreased cyclic ovarian function. The frequency of menstrual cycles decreases (oligomenorrhea), and the cycle may even cease (amenorrhea) altogether. Symptoms of estrogen deficiency, such as loss of sexual desire, dryness of the vagina, infertility, and, less often, abnormal lactation (galactorrhea) also occur. High serum prolactin concentrations are not usually associated with any symptoms in postmenopausal women, although in very rare cases galactorrhea may occur. In men, high serum prolactin concentrations also decrease gonadotropin secretion but therefore decrease testicular function, resulting in low serum testosterone concentrations. The major symptoms are loss of sexual desire, erectile dysfunction, muscle weakness, and infertility.

Prolactinomas are the most common type of hormone-secreting pituitary tumour. They are four to five times more common in women than in men. However, prolactinomas tend to be larger in men at the time of diagnosis. This difference is explained by the fact that menstrual irregularity is a very sensitive indicator of excess prolactin secretion, whereas decreased testicular function in men is not. Prolactinomas often cause headaches, disturbances in vision, and symptoms and signs of other pituitary hormone deficiencies.

Most patients with a prolactinoma are treated with drugs that mimic the action of dopamine, such as bromocriptine and cabergoline. These drugs result in a prompt decrease in prolactin secretion and a decrease in tumour size. In some cases, however, the drugs are not effective or may cause unacceptable side effects such as nausea, vomiting, and headaches. These patients may be treated by surgery or radiation therapy. Patients with few symptoms—for example, an occasional missed menstrual period—may not require treatment. These patients tend to have tumours that do not grow and tend to have mild hyperprolactinemia that does not increase. Dopamine-like drugs also lower prolactin secretion in patients with hyperprolactinemia from other causes, although it is preferable to remove the offending cause if it can be identified.

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